This invention relates to novel .alpha., .omega.-bis-(disubstitutedphosphino) hydrocarbon compounds, digold (I), digold (III), disilver (I) or dicopper (I) complexes thereof, pharmaceutical compositions containing, as an active ingredient, .alpha.,.omega.-bis(disubstituted-phosphino)hydrocarbon compounds or [.alpha., .omega.-bis(disubstituted-phosphino)hydrocarbon] digold (I), digold (III), disilver (I) or dicopper (I) compounds which have antitumor activity. In addition, this invention relates to a method for treating tumors by administering tumor-inhibiting amounts of said active ingredient to a host animal. As disclosed more fully below, the active ingredients are cytotoxic to mammalian cells in vitro, for example B16 melanoma cells, and tumoricidal against animal tumors in vivo, for example P388 leukemia tumors.
Vaughan, U.S. Pat. No. 3,661,959, issued May 9, 1972, discloses the preparation of Au, Au'-dichloro [methylenebis(diphenylphosphine)] gold (I) (Example 21) and Au, Au'-dichloro[ethylenebis(diphenylphosphine)] for these compounds is disclosed or suggested by the Vaughan reference. Weinstock et al., J. Med. Chem., 7(1), 139-140 (1974), discloses .mu.-[1,2-bis (diphenylphosphino) ethane] bis [chlorogold (I)] as an intermediate in the preparation of a polymeric compound, designated as Compound 5. Compound 5 was tested, but found to be ineffective as an oral antiarthritic agent. There is no disclosure or suggestion in the Weinstock reference that the intermediate has antiarthritic or any other type of pharmaceutical activity. Mc Auliffe et al., J.C.S. Dalton, 1730-1735 (1979), disclose physical and chemical data for several [.alpha..omega.-bis(disubstitutedphosphino) hydrocarbon] digold (I) compounds in Tables 1 and 4. However, there is no disclosure or suggestion in the Mc Auliffe reference that such compounds have any pharmaceutical activity. Marsich et al., J. Inorg. Nucl. Chem., 34, 933-949 (1972), disclose .mu.-[1, 2-Bis(diphenylphosphino) ethane ] bis [chlorocopper (I)]. However, there is no disclosure or suggestion in this reference that this compound has any pharmaceutical activity. Levason et al., Inorg. Chim. Acta, 8, 25-26 (1974), discloses .mu.-[1, 2-Bis (diphenylphosphino)alkyl] bis [nitratosilver (I)] compounds, wherein alkyl is methane, ethane, propane and ethylene. However, there is no disclosure or suggestion in this reference that these compounds have any pharmaceutical activity. DeStefano et., Inorg. Chem., 10, 998-1003 (1971), disclose .mu.-[1, 2-Bis(diphenyl-phosphino)ethane] bis[thiocyanatogold(I)]. However, there is no disclosure or suggestion in the DeStefano reference that this compound has any pharmaceutical activity. Struck et al., J. Med. Chem., 9, 41-416 (1966), disclose alleged cytotoxic activity for ethylenebis(diphenylphosphine) which is the active ingredient in some of the pharmaceutical compositions and methods of treatment of the instant application, and is also used as an intermediate in the preparation of some of the metal complexes of the instant invention. However, there is no disclosure or suggestion in the Struck reference of such metal complexes, or that they would display cytotoxic or any other pharmaceutical activity.